Hsp70 machinery vs protein aggregation: the role of chaperones in cellular protein homeostasis

Despina Serlidaki

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    Many neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's or ALS, but also some muscle degenerative diseases, have as a common characteristic the appearance of protein aggregates in the neuronal or muscular cells. As part of a greater protein quality control network in our cells, there are some proteins that are called molecular chaperones, that have been shown to have a protective function against aggregation. There are many different types of these proteins that combine to safeguard the proteins from aggregation. It is not known however how these chaperones do that. We show here that there is a high level of specialization in these chaperones and that different aggregating proteins that are associated with different diseases have a different handling by these chaperones. We identify in a molecular level how interactions between the chaperones can determine the way they work against aggregation. Moreover, by using known genetic mutations of chaperones that have been found to cause a degenerative disease called limb girdle muscular dystrophy, we aim to better understand the cause of the disease and the way these chaperones work in a molecular level. Overall, the work presented in this thesis outlines the importance of chaperones for the cell, to avoid relevant diseases like Alzheimer's, Parkinson's, Huntington's or ALS and many more. More importantly, it highlights the very high level of complexity and specialisation that occurs in these chaperone networks and the importance of understanding them in order to potentially use them preventively or therapeutically for the associated diseases.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    Begeleider(s)/adviseur
    • Kampinga, Harrie, Supervisor
    Datum van toekenning16-sep-2019
    Plaats van publicatie[Groningen]
    Uitgever
    Gedrukte ISBN's978-94-034-1872-8
    Elektronische ISBN's978-94-034-1871-1
    DOI's
    StatusPublished - 2019

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